Treatment of a metabolic liver disease in mice with a transient prime editing approach.

ABSTRACT: Prime editing is a versatile genome editing technology that circumvents the need for DNA double-strand break formation and homology-directed repair, making it particularly suitable for in vivo correction of pathogenic mutations. Here we developed liver-specific prime editing approaches with temporally restricted prime editor (PE) expression. We first established a dual-delivery approach where the prime editor guide RNA is continuously expressed from adeno-associated viral vectors and only the PE is transiently delivered as nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNP). This strategy achieved 26.2% editing with PEmax and 47.4% editing with PE7 at the Dnmt1 locus using a single 2 mg kg^-1 dose of mRNA-LNP. When targeting the pathogenic Pah^enu2 mutati

SUBMITTER: Rothgangl T 

PROVIDER: S-EPMC12532708 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature